New antiviral antibiotics; xanthocillin X mono- and dimethylether, and methoxy-xanthocillin X dimethylether. II. Biological aspects of antiviral activity. (Studies on antiviral and antitumor antibiotics. VI).

Effects of XME, XDE and XTE (xanthocillin X monoand dimethylether, and methoxy-xanthocillin X dimethylether) on multiplication of Newcastle disease virus (NDV) and on proliferation of chick embryo fibroblast cells (CEF) were examined. At low multiplicity, XME, XDE and XTE suppressed CPE at low concentrations. At high multiplicity, XME (10 mcg/ml) completely inhibited occurrence of CPE and syntheses of HA and infective virus, and at lower concentrations there was no difference in final yields of HA at 23 hours post infection, but a concentration dependency was found in synthesis of HA and suppression of CPE. XDE and XTE, on the other hand, did not inhibit HA synthesis completely at high concentration, but delayed the onset of HA production and partially arrested the occurrence of CPE post infection. All three antibiotics had very low toxicity against both grown and growing primary CEF. They also had no effect on free NDV particle and on viral adsorption ontoCEF. Searching for antiviral antibiotics, we found acetone extract of two strains of soil fungi exerted remarkable antiviral activity against Newcastle disease virus (NDV) and vaccinia and herpes simplex viruses in agar diffusion-plaque inhibition method, and isolated the active principles in crystalline form. They were identified as xan thocillin X monoand dimethylether, and methoxy-xanthocillin X dimethylether (XME, XDE and XTE, respectively)1'^. The three antibiotics had low cytotoxicity against primary culture of chick embryo* fibroblast cells (GEF) at higher concentrations than that required for suppression of occurrence of cytopathic effect (CPE) following viral growth. Their antiviral activity was studied employing NDV and primary culture of CEF virus-cell system. The present paper reports the effect on cell growth, on free virus particle and a adsorp tion of NDV onto CEF and also the antiviral activity determined by tube assay method of these antibiotics. Materials and Methods